Neural Control of Movement This project is devoted to understanding the nature of neuronal and muscular mechanisms required for clear vision. Our interest in normal behavior is refined by a focus on problems that lead to clinical eye movement disorders and misalignment of the two eyes (strabismus). Recent studies have shown that systems for vision and action interact, and thus a fuller understanding of our visual system requires study of both motor and sensory systems. We are looking into the network of areas that are involved in action and perception to understand how they may be coupled. One area that is important for making decisions about which target to select is the basal ganglia, and another is the cerebellum. We are studying patients with cerebellar deficits (e.g., spinal cerebellar ataxia) and basal ganglia deficits (e.g., Parkinson's disease). This should give us a clearer understanding of how these important brain areas cooperate to select the goal of an eye movement. Eye-Head Coordination Gaze saccades (coordinated eye and head movements) could be controlled by a single gaze controller, with eye and head movements sharing a common motor drive. Alternatively, gaze could be controlled by coupling together separate controllers for the eye and the head. However, experimental evidence has shown that eye and head trajectories can be decoupled by changes in initial eye and head position. This evidence has led us to propose a new model of gaze saccades based on two separate controllers, one for gaze and one for head, but without a separate controller for the eye. This new model has a novel architecture that can be used to control systems with any number of hierarchical links, such as eye-head-body. Clinical Eye Movement Disorders We have looked at several clinical eye movement disorders. Our recent models of brain stem neurons include the biophysical properties of voltage- and ligand-dependent ion channels. This has enabled us to model many eye movement disorders. In the past, we have used models of neurons that represented their state as a continuous variable (i.e., the cell's membrane potential). Now, we are using spiking neurons that communicate more like real neurons. We are starting with a model of the brain's mathematical integrator, using both excitatory and inhibitory channel receptors with different time courses. This approach has yielded a new method for determining the weights in the network. Visual Perception Strabismus, the abnormal alignment of the two eyes, is an important clinical problem. Proper coordination of the eyes relies on a cortical neural circuitry that is capable of extracting matching features in the images from each eye. This process, which is usually compromised in most cases of congenital strabismus, is quite complex, since each visual neuron sees only a tiny part of the whole image. To elucidate the mechanisms underlying binocular feature matching we have carried out several experiments in normal human subjects, using ever more sophisticated visual stimuli. In doing so we have discovered that multiple computations are carried out in parallel, and have quantified their differences and synergies. The investigation of these mechanisms in strabismic subjects will allow us to more objectively estimate their binocular deficits, and evaluate their time course and sensitivity to therapy. Another important aspect of vision is that it takes time to perceive a new object. When the new object appears in a peripheral location it is common for an eye movement to bring the image of the object onto the fovea (the area of highest visual acuity). It seems obvious that perception and action should be tightly coupled in time. There is no point in looking at an object you can't perceive, and vice versa. Nonetheless, the pathways for vision and action are different, and whether or how they may be coupled remains unknown. We have been studying the saccadic reaction time, the perceptual reaction time, and what is perceived by human subjects. Surprisingly, we find that all three share a common time course, suggesting that they may be sharing the same trigger for their response.